Polypoidal choroidal vasculopathy and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome can have ocular complications. We report a 44-year-old Chinese lady with recurrent relapses of SLE and antiphospholipid syndrome with high disease activity, presenting with visual distortion in her right eye for 2 months. There was subretinal hemorrhage in her right eye, confirmed on investigations to be choroidal neovascularization secondary to a variant of age-related macular degeneration known as polypoidal choroidal vasculopathy (PCV). Anti-vascular endothelial growth factor therapy resolved her eye condition. SLE could be associated with PCV via common mechanisms, including complement pathway activation and vasculitis involving the choroidal circulation.

Stealth liposomes: an improved sustained release system for 1-beta-D-arabinofuranosylcytosine.

Newly developed liposomes with prolonged circulation half-lives and dose-independent pharmacokinetics (Stealth liposomes) have been tested for their efficacy as a slow release system for the rapidly degraded, schedule-dependent, antineoplastic drug 1-beta-D-arabinofuranosylcytosine (ara-C) in the treatment of murine L1210/C2 leukemia. Mice were given injections of either 10(5) cells or 10(6) cells by either the i.v. or the i.p. routes. Leukemia-bearing mice were treated with either i.v. or i.p. injections of free drug, i.v. or i.p. injections of liposome-entrapped drug, or 24-h i.v. infusions of free drug. Long-circulating liposomes contained, as the stealth component, either monosialoganglioside or polyethylene glycol-distearoylphosphatidylethanolamine. Liposomes lacking the stealth components (non-stealth liposomes) were also injected for comparison. At lower dose ranges, stealth liposomes were superior to non-stealth liposomes in prolonging mean survival times of the mice, and all liposome preparations were superior to injections of the free drug. Drug entrapped in stealth liposomes, when administered at or near the maximum tolerated dose of 100 mg/kg ara-C were considerably superior to 24-h free drug infusions given at the same total drug dose. Therapeutic effect was related to the half-life of leakage of ara-C from the liposome formulations, as well as to circulation half-life, with maximum therapeutic effect achieved with long circulation half-lives and more rapid leakage rates. The therapeutic efficacy of non-stealth liposomes increased with increasing liposome (and drug) dose as a result of saturation of liposome uptake by the mononuclear phagocyte system, which resulted in longer circulation half-lives for these liposomes at higher doses (Michaelis-Menten pharmacokinetics). Liposome entrapment can protect rapidly degraded drugs from breakdown in vivo, with release of the drugs in a therapeutically active form over periods of up to several days. The dose-independent pharmacokinetics and reduced mononuclear phagocyte system uptake of stealth liposomes gives them distinct advantages over non-stealth liposomes.

Calmodulin content in rabbit reticulocyte and the influence of opioid peptides on calmodulin activity in its membrane.

Calmodulin (CaM) content in rabbit reticulocyte and the influence of opioid peptides on CaM activity in its membrane were studied by a highly sensitive assay of CaM activity based on the stimulation of Calcium-dependent phosphodiesterase activity. The CaM contents in reticulocytes were higher than those in normal erythrocytes, both in the cytosol fraction and in the membrane fraction. Among the opioid peptides, beta-endorphin (beta-EP) and dynorphin-A-(1-13) (dyn) had a significant inhibitory effect on CaM activity in reticulocyte membrane. The effect was not antagonized by naloxone or Mr. 2266, nor influenced by increase of Ca2+ concentration, but was reversed by the addition of exogenous CaM. This implies that the action of beta-EP and dyn on reticulocyte membranes probably involves an non-opioid mechanism, in which CaM may be an important key of linkage.

Anti-idiotypic antibodies raised against anti-metenkephalin antibodies in rabbits.

Anti-idiotypic antibodies were raised in rabbits immunized against immunoglobulins purified from anti-metenkephalin antibody. The antibodies competed dose-dependently with metenkephalin in binding to anti-metenkephalin antibody on a solid phase metenkephalin enzyme-linked immunosorbent assay (ELISA). The titers of the antiidiotypic activity appeared characteristically in transient peaks and troughs in alternation with anti-metenkephalin activities and were retained after purification on various affinity columns.